Role of endogenous angiotensin II on sympathetic reflexes in conscious rabbits.

In the present study we sought to determine the contribution of endogenous brain stem angiotensin to renal sympathetic reflexes in conscious rabbits. Initial studies determined the subtype of receptor involved in the pressor response to angiotensin II (ANG II) administration into the fourth ventricle (4V). The AT1 antagonist losartan (0.001-10 micrograms 4V) had no effect on blood pressure alone but caused a dose-dependent blockade of the pressor effect of ANG II, with complete blockade produced by 10 micrograms, an effect that lasted for at least 3 h. The AT2 antagonist PD-123319 (0.1-1,000 micrograms) and vehicle had no effect on the ANG II pressor response. The effect of losartan (10 micrograms) on the baroreceptor, chemoreceptor, and trigeminal reflexes was examined in eight rabbits that had been implanted with 4V catheters and an electrode for recording renal sympathetic nerve activity (RSNA) 1 wk earlier. Baroreflex assessments were made during normoxia and two conditions of hypoxia (10% O2 and 10% O2 + 3% CO2) before and after 10 micrograms losartan or vehicle, on separate experimental days. During normoxia and hypoxia+CO2 losartan increased resting RSNA, the range, and upper plateau of the RSNA-MAP baroreflex curves. By contrast the marked increase in RSNA due to activation of trigeminal afferents was not affected by losartan. In conclusion the effect of losartan to increase RSNA activity in conscious rabbits, particularly during hypoxia and baroreceptor unloading, suggests that endogenous ANG II via AT1 receptors normally inhibits renal sympathetic baroreceptor and chemoreceptor reflexes.

Frequency and amplitude of sympathetic discharges by baroreflexes during hypoxia in conscious rabbits.

Sympathetic nerve activity (SNA) from multifiber preparations exhibits two distinct components: the frequency at which discharges occur and their relative amplitude (reflecting the number of activated nerve fibers within each burst). These two components may respond independently to various afferent inputs, indicating separate central controlling processes. We examined the response in the frequency and amplitude of renal SNA to changes in baroreceptor activity and the effect of two forms of hypoxia on this relationship in nine conscious rabbits. Rabbits breathed either room air or one of two hypoxic gas mixtures (10% O2 or 10% O2 + 3% CO2) for 20 min, during which baroreflexes were stimulated by ramp increases and then decreases in arterial pressure with phenylephrine (0.5 mg/ml iv) and nitroprusside (1 mg/ml) (total arterial pressure range induced was 80 mmHg). Hypoxia with 10% O2 significantly increased the resting frequency of SNA before baroreflex modifications from 2.15 +/- 0.18 to 2.82 +/- 0.25 discharges/s and with 10% O2 + 3% CO2 to 3.20 +/- 21 discharges/s. The amplitude of sympathetic discharges was increased 44 +/- 5% over control levels during 10% O2 but was not further increased by the addition of 3% CO2. The baroreflex curve for total SNA (1-s averages of the integrated neurogram) showed a graded response to the two hypoxic stimuli, with significant increases in the upper plateau, gain, and resting point on the curves. However, the baroreflex curve for the frequency or amplitude of sympathetic discharges did not show graded responses to each hypoxic treatment. The frequency baroreflex curve was sigmoidal and not changed from air during 10% O2. During 10% O2 + 3% CO2, the gain (responsiveness) of the curve was increased although the range of frequencies occurring was unaltered. The baroreflex curve for the amplitude showed similar responses to the two hypoxic stimuli, namely, increases in the upper plateau, gain, and resting point of the curve. We conclude that the frequency and amplitude of sympathetic discharges are able to respond differentially to changes in afferent stimuli. Given that alterations in the frequency and recruitment of sympathetic fibers (amplitude) to the kidney may have differing effects, this phenomenon may provide a previously unknown level of renal hemodynamic control through the interaction of specific afferent inputs to the central nervous system.

Medullary neurons activated by angiotensin II in the conscious rabbit.

Previous studies have shown that angiotensin II (Ang II) can activate cardiovascular neurons within the medulla oblongata via an action on specific receptors. The purpose of this study was to determine the distribution of neurons within the medulla activated by infusion of Ang II into the fourth ventricle of conscious rabbits, using the expression of Fos, the protein product of the immediate early gene c-fos as a marker of neuronal activation. Experiments were done in both intact and barodenervated animals. In comparison with a control group infused with Ringer's solution alone, in both intact and barodenervated animals, fourth ventricular infusion of Ang II (4 to 8 pmol/min) induced a significant increase in the number of Fos-positive neurons in the nucleus of the solitary tract and in the rostral, intermediate, and caudal parts of the ventrolateral medulla. Double-labeling for Fos and tyrosine hydroxylase immunoreactivity showed that 50% to 75% of Fos-positive cells in the rostral, intermediate, and caudal ventrolateral medulla and 30% to 40% of Fos-positive cells in the nucleus of the solitary tract were also positive for tyrosine hydroxylase in both intact and barodenervated animals. The distribution of Fos-positive neurons corresponded very closely to the location of Ang II receptor binding sites as previously determined in the rabbit. The results indicate that medullary neurons activated by Ang II are located in discrete regions within the nucleus of the solitary tract and ventrolateral medulla and include, in all of these regions, both catecholamine and noncatecholamine neurons.